Proteins

Describe the various functions of proteins

1. Homeostatic: Soluble proteins in the blood plasma act as buffers to stabilise the pH in the blood.

2. Enzymatic: Protein enzymes catalyse chemical reactions to increase the rate of reaction.

3. Support: Collagen is a major component of connective tissues, cartilage, tendons and ligaments. Keratin is present in hair, hoofs and feathers.

4. Transport: Proteins in the plasma membrane transport water-soluble substances in and out of the cell/ membrane-bound organelle. Haemoglobin transports oxygen in vertebrates. Lipoproteins transports cholesterol in the blood.

5. Hormonal: Hormones such as insulin and glucagon.

6. Signalling within cells and communication between cells: G-protein coupled receptors are involved in transmitting signals from the external environment to the internal environment of the cell. Relay proteins such as Ras protein and protein kinases are involved in the signalling pathway within a cell.

7. Protection: Antibodies of the immune system. Blood clotting factors such as fibrinogen and thrombin.

8. Storage: Ferritin stores iron in the liver. Myoglobin stores oxygen in skeletal muscle cells.

9. Source of energy: Proteins act as a source of energy during extreme starvation when carbohydrates and fat reserves are depleted.

State the various types of amino acids

1. Polar amino acids such as cysteine and serine have polar R groups.

2. Non-polar amino acids such as glycine and proline have non-polar R groups.

3. Acidic amino acids such as aspartic acid and glutamic acid are negatively charged and their R group contains at least one carboxyl group.

4. Basic amino acids such as lysine and arginine are positively charged and their R group contains at least one amino group.

Describe how peptide bonds are formed

1. A peptide bond is formed via a condensation reaction between the carboxyl group of one amino acid and the amino group of the next amino acid with the removal of one molecule of water.

2. The reaction is catalysed by enzyme peptidyl transferase on the large ribosomal subunit.

Describe how peptide bonds are broken

1. A peptide bond is broken via a hydrolysis reaction with the addition of one molecule of water.

2. This reaction is catalysed by enzyme protease such as trypsin and chymotrypsin.

Describe the primary structure of proteins

1. The primary structure is the number and sequence of amino acids in a polypeptide chain. It is stabilised by peptide bonds between amino acids residues.

2. A slight change in the primary structure of a protein can alter its properties drastically as it affects the subsequent levels of protein structure.

Describe the secondary structure in proteins

1. The secondary structure is the localised repetitive folding of the polypeptide chain. It is stabilised by hydrogen bonds between peptide linkages of the polypeptide backbone.

2. There are two main types of secondary structures: alpha helix and beta pleated sheets.

Describe the structure of alpha helix

1. The alpha helix takes the form of an extended spiral spring.

2. It is stabilised by hydrogen bonds between -C=O and -NH groups (peptide linkages) within the polypeptide chain.

3. There are 3.6 amino acids per complete turn of the alpha helix.

4. A protein which is almost entirely alpha-helical is keratin.

Describe the structure of beta pleated sheets

1. Two or more regions of the polypeptide chain lie parallel to each other in flat zig-zagged sheets.

2. It is stabilised by hydrogen bonds between -C=O group of one part of the chain and -NH group of another part of the chain.

3. Each region is known as a beta strand.

4. Beta strands may run in the same direction to form parallel beta pleated sheets or run in opposite directions to form anti-parallel pleated sheets.

5. An example of a protein which is almost entirely made of beta pleated sheets is fibroin found in silk.

Describe the tertiary structure of proteins

1. The tertiary structure is where the polypeptide chain folds and bends into a precise globular three-dimensional shape unique to the protein. It is stabilised by four types of bonds between R groups of amino acid residues at different regions of the polypeptide chain namely hydrophobic interactions, hydrogen bonds, ionic bonds and disulfide bonds.

Describe the quaternary structure of proteins

1. The quaternary structure is the combination of more than one polypeptide chain to form a large protein molecule. It is stabilised by four types of bonds between R groups of amino acid residues of the different subunits namely hydrophobic interactions, hydrogen bonds, ionic bonds and disulfide bonds.

Describe the various functions of haemoglobin

1. Haemoglobin transports oxygen in the blood.

Describe the structure of haemoglobin

1. Haemoglobin is found in the cytoplasm of red blood cells.

2. It has a quaternary structure.

3. It is a tetramer consisting of four separate polypeptide chains, two alpha chains and two beta chains.

4. It is a conjugated protein consisting of a protein component globin and a non-protein component haem group

Describe how the structure of haemoglobin contributes to its function

1. Each subunit is folded into a 3D globular shape where hydrophobic amino acid residues are buried in the interior while hydrophilic amino acid residues are on the exterior. This feature is related to the tertiary structure. Therefore, haemoglobin is soluble in water and is a suitable transport protein.

2. Each subunit contains a haem group which consists of a porphyrin ring and an iron ion. The haem group binds to oxygen. Therefore, oxygen binds reversibly to haem group to transport oxygen. Oxygen is able to dissociate when blood flows to oxygen-deprived tissues.

3. Each haemoglobin molecule has four haem groups. This feature is related to the quaternary structure. Therefore, one haemoglobin molecule can carry up to four oxygen molecules.

4. The four subunits are stabilised by non-covalent interactions namely hydrophobic interactions and hydrogen bonds. This feature is related to the quaternary structure. Therefore, the structural arrangement of the four subunits allows for cooperative oxygen binding where the binding of one oxygen molecule to haem group of one globin subunit triggers a conformational change in the other three globin subunits. This increases the affinity of the other globin subunits to oxygen and faster uptake of oxygen by subsequent haem groups in the same haemoglobin molecule.

Describe the various effects of the DNA substitution in sickle cell anaemia

1. In sickle cell anaemia, a single nucleotide substitution mutation occurs in the gene coding for the beta globin chain.

2. The nucleotide thymine is replaced by adenine in the DNA template strand.

3. The 6th codon in the mRNA is changed.

4. The amino acid glutamic acid is replaced by valine in the polypeptide chain.

5. The R group of glutamic acid is hydrophilic while that of valine is hydrophobic.

6. This change results in the formation of a mutated haemoglobin molecule (HbS).

7. HbS has a hydrophobic region on the surface of the protein due to the hydrophobic amino acid residue valine.

8. In low oxygen concentrations, Hbs haemoglobin molecules interact with each other via hydrophobic interactions to crystallise into rod-like fibres.

9. Hence, HbS is less efficient in carrying oxygen which leads to anaemia.

10. The rod-like fibres of HbS distort the normal circular, biconcave disc shape of the red blood cell into a sickle shape which blocks blood vessels.

Describe the various effects of sickle cell anaemia

1. Sickle cell anaemia interferes with blood circulation and deprives organs of oxygen.

2. Hence, organs become damaged and this may lead to death.

3. The sickle-shaped red blood cells also have a shorter life span and are brought to the spleen to be destroyed.

4. The spleen may become enlarge due to the accumulation of sickle-shaped red blood cells.

Explain why haemoglobin can release oxygen in areas with high rate of respiration

1. The ability of haemoglobin to pick up or release oxygen depends on the partial pressure of oxygen (pO2) and partial pressure of carbon dioxide (pCO2) in its environment.

2. In respiring tissues with low pO2 and high pCO2, haemoglobin releases oxygen.

3. Carbon dioxide produced forms carbonic acid.

4. pH decreases and cause haemoglobin to release more oxygen.

5. Bohr’s effect is observed.

Describe the various functions of collagen

1. Collagen is a major component of connective tissues and provides strength and resilience to tissues.

Describe the structure of collagen

1. Collagen is a fibrous protein.

2. It has a quaternary structure.

3. The basic unit of collagen is tropocollagen.

4. Three polypeptide chains wrap around each other to form a triple helix with each polypeptide chain having a unique secondary structure which has 3.3 amino acid residues per complete turn.

Describe how the structure of collagen contributes to its function

1. Each polypeptide chain has about 1000 amino acid residues. It consists mainly of repeated glycine-X-Y sequences. X can be proline and Y can be hydroxyproline. Glycine occurs more frequently. This feature is related to the primary structure. Therefore, this repeating organisation contributes to a stable helical structure.

2. Every third amino acid in the polypeptide is glycine. The R group of glycine is a H atom and it is the only R group small enough to fit into the centre of the triple helix. This feature is related to the primary structure. Therefore, the three polypeptide chains are closely associated.

3. The localised repetitive folding of each polypetide chain forms a helix. Hydrophobic R groups of proline and hydroxyproline project on the exterior of the triple helix. This feature is related to the primary structure. Therefore, collagen is an insoluble and is a suitable structural protein.

4. The three helical chains wound around each other to form a triple helix. This feature is related to the quaternary structure. The chains are held together by interchain hydrogen bonds between the -NH groups of glycine residues on one chain and -C=O groups of proline residues on another chain. Therefore, this stabilises the fibrous structure of tropocollagen and cause it to be rigid. It enables collagen to have high tensile strength.

5. The tropocollagen molecules lie parallel to each other with a staggered arrangement and are joined by covalent cross-links between C and N terminals between tropocollagen. This forms collagen fibrils which further assemble to form collagen fibres. The longitudinal displacement/ staggered arrangement of the collagen molecules gives rise to the banded appearance of the collagen fibril. Therefore, this gives additional rigidity and tensile strength to collagen.

Describe how collagen fibrils begin in the rough endoplasmic reticulum and is completed outside the cell

1. The triple helix structure is formed in the lumen of the rER and completed in the GA.

2. Hydroxylation, glycosylation and disulfide bond formation occurs in the rER.

3. Tropocollagen subunits then spontaneously self-assemble with regularly staggered ends to form collagen fibrils outside the cell.

State the various differences between fibrous and globular proteins

1. In fibrous proteins, the secondary structure is the most important while in globular proteins, the tertiary structure is the most important.

2. In fibrous proteins, polypetide chains form long fibres/ sheets which are more regular and stable while in globular proteins, polypeptide chains tightly fold to form a globular shape which are less regular and unstable.

3. In fibrous proteins, length of the chain may vary in two samples of the same protein while in globular proteins, length of the chain is always identical in two samples of the same protein.

4. Fibrous proteins are insoluble in water while globular proteins are soluble in water to form colloidal solutions.

5. Fibrous proteins have supportive functions such as maintaining structure and providing support while globular proteins have many functions such as enzymatic and hormonal.

6. Examples of fibrous proteins are collagen, keratin and fibrion while examples of globular proteins are enzymes and haemoglobin.